富含大脑的编码和长非编码 RNA 基因在复发性神经发育障碍 CNVs 中过度表达。
Brain-Enriched Coding and Long Non-coding RNA Genes Are Overrepresented in Recurrent Neurodevelopmental Disorder CNVs.
机构信息
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, 6009 WA, Australia; Systems Biology and Health Data Analytics Lab, The Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, 2052 NSW, AU.
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, 6009 WA, Australia; Curtin Health Innovation Research Institute, Curtin University, Bentley, 6845 WA, Australia.
出版信息
Cell Rep. 2020 Oct 27;33(4):108307. doi: 10.1016/j.celrep.2020.108307.
Autism spectrum disorder (ASD) is a neurodevelopmental condition with substantial phenotypic and etiological heterogeneity. Although 10%-20% of ASD cases are attributable to copy number variation (CNV), causative genomic loci and constituent genes remain unclarified. We have developed SNATCNV, a tool that outperforms existing tools, to identify 47 recurrent ASD CNV regions from 19,663 cases and 6,479 controls documented in the AutDB database. Analysis of ASD CNV gene content using FANTOM5 shows that constituent coding genes and long non-coding RNAs have brain-enriched patterns of expression. Notably, such enrichment is not observed for regions identified by using other tools. We also find evidence of sexual dimorphism, one locus uniquely comprising a single lncRNA gene, and correlation of CNVs to distinct clinical and behavioral traits. Finally, we analyze a large dataset for schizophrenia to further demonstrate that SNATCNV is an effective, publicly available tool to define genomic loci and causative genes for multiple CNV-associated conditions.
自闭症谱系障碍（ASD）是一种神经发育障碍，具有显著的表型和病因异质性。尽管 10%-20%的 ASD 病例可归因于拷贝数变异（CNV），但致病基因组位和组成基因仍不清楚。我们开发了 SNATCNV，这是一种优于现有工具的工具，从 AutDB 数据库中记录的 19663 例病例和 6479 例对照中鉴定出 47 个常见的 ASD CNV 区域。使用 FANTOM5 对 ASD CNV 基因含量进行分析表明，组成编码基因和长非编码 RNA 具有丰富的脑表达模式。值得注意的是，使用其他工具鉴定的区域没有观察到这种富集。我们还发现了性二态性的证据，一个独特的包含单个 lncRNA 基因的位点，以及 CNV 与不同的临床和行为特征的相关性。最后，我们分析了一个大型的精神分裂症数据集，以进一步证明 SNATCNV 是一种有效的、公开可用的工具，可用于定义与多个 CNV 相关疾病的基因组位和致病基因。
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